Transcript Chapter 12 Individual Genetic Variation and Gene Regulation

Chapter 12
Individual Genetic Variation
and Gene Regulation
Xodar
Figure CO: Kittens
© twobluedogs/ShutterStock, Inc.
Overview
• Natural selection acts on existing
phenotypic variation
• Mutations are necessary for evolution
– multiple alleles, gene duplications,
alterations in chromosome number,
transposable elements, and modification
of regulation all contribute to variation
• Mutations
– In Structural genes and Regulatory genes
Variation: Central Questions
• What is the relationship between the genetic
variation of the genotype and variation of the
phenotype?
• genotype + gene regulation + gene interactions
within the genome + developmental processes +
environmental effects and constraints + randomvariation → phenotype
Variation: Central Questions
• What are the
mechanisms by which
mutations and
modifications of gene
regulation serve as
sources of variation?
Variation: Central Questions
• What other sources of variation are available to
populations?
– Chapter 13: gene flow and random mutation
• What are the ecological and developmental
determinants of phenotypic variation?
– Chapter 14: body size, geographic range, home range
size, niche width, lifespan, environmental stress,
population size and density, etc.
Mutations Have Many Causes
• Spontaneous Mutations
– DNA copy errors
• Induced Mutations
–
–
–
–
Mutagens
Radiation
Viruses
Transposons
• Somatic Mutations
• Germline Mutations
Mutations and Health
A Service of the U.S.
National Library of Medicine
POLYPOLOIDY (ENTIRE SETS OF
CHROMOSOMES
UK Science Museum Short Animation
Mutations in the Genome
• Point mutations can occur through:
– substitutions (change in bases)
including tautomer errors
– insertions (introduction of bases)
– deletions (loss of bases) within the
DNA
– or change in gene position:
transpositions
Mutations in the Genome
• Major transposition of DNA segments can produce
chromosomal inversions
• Segments of DNA can be rearranged to new locations
and even to other chromosomes producing
chromosomal translocations
Mutation From a Functional Perspective
1. Sense Mutation: There is a change in the DNA
base sequence but no change in amino acids in
the polypeptide structure
2. Missense Mutation: There is a change in the DNA
base sequence, and a change in amino acids in the
polypeptide structure, but the protein is still
functional to some degree
3. Nonsense Mutation: There is a change in the
DNA base sequence and a change in amino acids
in the polypeptide structure, and the protein is
non-functional, a fragment, or is not produced at
all
Transitions and Transversions
Point
Mutations
Transitions outnumber
Transversions 2:1
Tautomers of Nitrogenous Bases
Point Mutations
• Silent or synonymous
– Silent mutations are
much more likely when
the point mutation is in
the third position of the
codon triplet
Point Mutations
• Replacement or
nonsynonymous
• Stop codon
Pleiotropic Effects
• Most genes have multiple or pleiotropic effects
• A given mutation has the potential to have a wide
variety of effects on reproductive fitness if the
individuals carrying the mutant allele are exposed
to a wide variety of environmental conditions or
selection pressures
• A given genotype may be adaptive in some
environments, neutral in others, and maladaptive in
still others
Pleiotropic Effects
Pleiotropic Effects:
Inborn Errors of Metabolism
Cystic fibrosis
Sickle Cell Is a Point Mutation
Sickle Cell is an Example of
An Inborn Error of Metabolism
For More on Sickle Cell
From Harvard University
Sickle Cell Disease
a) Normal: DNA codes via mRNA
for the amino acid, glutamic
acid, one of many proteins in
the hemoglobin molecule
b) Sickle cell disease: A single
base change in DNA codes via
RNA for a different amino
acid, valine
• But this critical amino acid is
important in proper folding of
the hemoglobin molecule,
which becomes defective,
producing sickled red blood
cells
Sickle Cell Anemia
widespread organ
damage
accumulates
over time
Figure 07: Sickle cell mutation
Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985.
Sickle Cell and Natural Selection
Heterozygote Superiority
Due to an alteration in potassium transport in the
red cells of individuals with some Hemoglobin S,
i.e., both homozygous recessives and
heterozygotes (carriers) for Hgb S, the malarial
parasite cannot complete its life cycle easily
inside these affected cells
Loss-of-Function Mutations
Insertion
Deletion
Stop Codon
 Frameshift mutations 
Transposons May
Cause Frameshift
Mutations
• “Jumping Genes” direct
the synthesis of additional
copies of themselves,
using transposase, which
are introduced into
neighboring regions of
DNA which exhibit a
particular target sequence
Variation in Chromosome Number
• Two major kinds of changes:
– number of entire sets of chromosomes
– numbers of single chromosomes within a set:
aneuploidy
• Repetitive doubling = polyploidy
Polyploidy
• Polyploidy occurs when there are more than two
homologous sets of chromosomes
• Most multicellular eukaryotic organisms are normally
diploid
• Polyploidy may occur due to abnormal cell division, i.e.,
nondisjunction events
• Polyploidy occurs in some animals, such as goldfish,
salmon, and salamanders, but is especially common among
ferns and flowering plants, including both wild and
cultivated species
Polyploidy: Changes in Sets of Chromosomes
Diploid cabbage species (Brassica
oleracea - R and B. rapa - L) were
crossed to produce the large,
vigorous tetraploid species,
Brassica napus.
 Failure of the spindle apparatus to separate
chromosomes is a non-disjunction event
Breeding an Artificial Tobacco
Species in the Laboratory
• Two diploid species, Nicotiana
tabacum (2n = 48) and N.
glutinosa (2n = 24) were
crossed
• The sterile triploid (2n = 36)
could be propagated
Figure 02: Flowers and
vegetatively
diploid gene numbers of
the tobacco plants
• An accidental chromosome
doubling then yielded a fertile
species, N. digluta, (2n = 72)
The Evolution of Wheat
• At least 30,000 years ago,
in the Fertile Crescent of
southwest Asia, a natural
hybrid formed between
two grasses, Triticum
monococcum (wild
einkorn) and a species of
Aegilops (goat grass)
Figure 01: Hybrid wheat
© R0b/Dreamstime.com
Triticum monococcum
Aegilops
The Evolution of Wheat
• Later, tetraploid Triticum sps. hybridized with a
diploid species to yield modern hexaploid wheat
Fig. 1. Wheat spikes showing (A) brittle rachis, (B to D)
nonbrittle rachis, (A and B) hulled grain, and (C and D)
naked grain.
J Dubcovsky, J Dvorak Science 2007;316:1862-1866
Published by AAAS
Polyploidy
• While rare, nondisjunction events do occur
• Since plants often make large numbers of gametes, low
probability events are more likely to occur
• If a diploid pollen grain fertilizes a diploid egg, a
tetraploid is born which is potentially reproductively
isolated from the start
• The incipient species can also reproduce vegetatively,
avoiding the mechanical conflicts in meiosis until there
are enough individuals to form a small interbreeding
polyploid population
The Polyploid Lifestyle
• Polyploid plants are often large and hardy, even more
vigorous and healthy than their diploid ancestors
• They may be better competitors in the common
environment and can increase their range at the
expense of the parent species
•
The Polyploid Lifestyle
• Sometimes, after generations,
the tetraploid population,
already reproductively isolated
from its parent diploid
population, accumulates
enough genetic (and
phenotypic) divergence to be
recognized as a distinct species
by scientists
• In fact, it may have been a
distinct biological species in
terms of its own life history
from the outset – in a single
generation
Triploidy
• In other circumstances, a
diploid gamete fertilizes a
normal haploid gamete
checkered whiptail lizard
3N
• Then a triploid individual
results
3N
3N
• At meiosis, sets of 3 like
chromosomes have great
mechanical difficulty during the
close alignment of synapsis
Triploidy
• Gametes are produced with chromosome numbers varying
from the 1N haploid number to the 2N diploid number
• Most of these gametes fail to produce viable offspring
when they combine at fertilization, but sometimes those
gametes that carry the 2N diploid number find and fertilize
other like 2N diploid gametes and a tetraploid individual or
population is produced after passing through this so-called
triploid bottleneck
Jefferson’s salamander
grass carp
The Polyploid Lifestyle
• Self-fertilization is common in
plants
• Certain hermaphroditic animal
species are capable of selffertilization
• Animals may also become
polyploid through
parthenogenesis, which is
reproduction by females without
fertilization by males
Parthenogenetic Species
The Polyploid Lifestyle
• Perhaps in later generations, some of these
polyploid individuals achieve a return to sexual
means of reproduction, but if not, asexual
reproduction may be enough to permit the
population to exist as a permanent community
• Natural selection may even encourage the evolving
population to return to sexual reproduction by
favoring those individuals who can both self-fertilize
and outcross, because those that can do both are
more likely to leave more descendants in future
generations
Polyploidy
• Modern molecular
techniques
(“clocks”) often
allow estimates of
times since
divergence for
polyploid series of
related species
cotton
Shifts Between
Sexual and Asexual Reproduction
green peach aphid
Myzus persicae
Daphnia
The Polyploid Lifestyle
• The polyploids have the advantage of duplications at every
locus
• Therefore, all the old blueprints for useful proteins
remain, while at the same time, another copy of all the
genetic blueprints are available to accumulate mutations
and develop novel proteins capable of performing new
functions for the plant
In this example, the spindle
apparatus broke down, leaving
a tetraploid cell that then
divided normally thereafter
The Polyploid Lifestyle
• In contrast to polyploid plants, polyploid animals
are often malformed and do not experience
normal development
• For example, it is well known from genetic studies,
karyotype studies, of still born humans and from
still born domestic animals, such as cows, horses,
sheep, goats, cats and dog, that many of the
naturally aborted fetuses were polyploids
triploid fetus
Human Triploids from
Spontaneous Abortions
Karyotype of 69,XXY (triploidy), common
finding in spontaneous abortion. Risk for
chromosomal anomaly in subsequent
pregnancy is not increased significantly.
syndactyly in triploid
Similar karyotype of 69,XXX (triploidy)
Animal Triploidy
• Some scientists speculate that the reason animals
do not tolerate polyploidy has to do with the
regulation of growth of a specific body plan
• In other words, an animal needs the right set of
bones in the right place, the right set of neurons in
the right place, the right set of muscles in the right
place, and so on
Severe intra-uterine
growth retardation in
maternal triploidy
• The animal body plan is very complex and
structural relationships must be matched precisely
for the parts to work together effectively
Human Triploids from
Spontaneous Abortions
• Some 1-2% of all human
conceptions may be triploid, but
most spontaneously abort
• These may account for as many as
25% of chromosomally abnormal
fetuses that spontaneously abort in
the first trimester
• The live birth rate is estimated at
1:2,500
• Triploidy is lethal – prenatally or
early in the newborn period
• However, rarely mosaicism occurs,
and these individuals may live for a
Triploidy - stillbirth at 39 weeks (69,XXX)
while, but they are associated with
- note the appearance of the hands
profound mental retardation and
other serious anatomical and
physiological abnormalities
 A different specimen
The Polyploid Lifestyle
• Plants, on the other hand, have fewer parts, fewer
organ systems, and can tolerate extremely divergent
structural relationships
• It is not crucial, for example, that plants be bilaterally
or radially symmetrical
The Polyploid Lifestyle
• The rootlets, the stems,
the leaves, and the flowers
do not all have to appear
at exactly the same places
on the stems or branches
of different individuals for
these individuals to be
viable, to be successful,
and to be reproductively fit
• This hypothesis is logical, but difficult to verify
Chromosome Alterations
• Potentially the largest phenomenon capable
of contributing to the pool of mutations
• Some chromosome changes affect only gene /
locus order and organization
• Others alter the amount of DNA available
• Others alter blueprints, eliminate genes, or
add copies of genes
• Others influence linkage groups of genes
Chromosome Rearrangements Occur
During Meiosis Division I Synapsis
Crossing Over and Recombination
• During meiosis, chromosomes duplicate and homologous
pairs synapse
• Chromatids exchange homologous sections carrying alleles,
producing recombinant daughter chromosomes with a
different combination of alleles
Equal and Unequal Crossing-Over
Figure 04: Equal and unequal crossing-over for three gene segments on a chromosome
• Equal Crossing-Over provides new arrangements of alleles on
chromosomes but has little potential for new variation
• Variation could occur if the break and repair occurred within a gene,
instead of between genes as illustrated
Chromosomal Rearrangements
a) Deletion: Part of a chromosome breaks off and is lost
b) Translocation: Part of a chromosome detaches and
becomes attached to another
c) Inversion: Part of a chromosome becomes switched
around within the chromosome
Unequal
CrossingOver
• During meiosis, synapsed chromosomes occasionally pair
out of register with each other
• Cross-over then occurs between non-homologous sections
• As a result, genes are duplicated on one chromosome, and
deleted on the other
• Chromosomes with gene duplications provide new
possibilities for gene function in eukaryotic evolution
Unequal Cross-Over and the Origin of
Gene Duplications
Gene duplications are the source of most new
genes, i.e., new loci, new blueprints
Free to
evolve a
new
function!
Remember that cross-over occurs during Meiosis, so this process
is primarily of benefit to sexually reproducing organisms
Chromosomes With
Duplications
 Gametes with sections of
duplication bring more than a
full set of normal genes to the
zygote at fertilization
 They bring a series of
duplicate loci
 One of the duplicated loci can
continue to produce the original
protein product while the other
duplicate locus can accumulate
mutations at no cost to the
organism
 If any of those mutations
confer an advantage, then
natural selection can go to work
to spread the mutant allele in
the population
Chromosome Inversion
Two breaks occur in a single DNA strand but the improper repair
reverses the sequence of the loci on one chromosome
The inversion has not altered the individual gene blueprints, just
their arrangement along the arm of the chromosome
Crossing-Over Changes
the Phenotype of
Chromosomes
inversion loops protect linked alleles
from being separated by crossing over
Figure 03: Structural chromosomal changes
Chromosomal Evolution in Drosophila
• Polytene chromosomes in
the salivary glands
provided an early methods
for mapping genes to
specific chromosomes
Inversions Cause Problems in Meiosis
The homologs cannot pair easily in this region because the sequences do not
match. When they do pair and cross-over occurs, the products include large
sections of duplication on one homolog and large sections of deletion on the
other. Gametes that get chromosomes with large sections deleted often lead
to failure of development in the resulting zygote.
Heterozygous Inversions Produce
Stable Linkage Groups
• There is a potential evolutionary
advantage to having an inverted
sequence
• Due to the odd physical pairing of the
chromosomes at meiosis, once an
inversion has become stabilized
somewhere along the length of the
chromosome in one of a pair of
homologs, while the other contains the
original sequence, further cross-over
events are mechanically unlikely
• So the alleles in the inverted region are
then protected and passed as a unit to
future generations
Heterozygous Inversions Produce
Stable Linkage Groups
• We call these individuals “heterozygotic” for the
inversion
• One chromosome carries the inversion while the
other homolog does not
• Alleles stay neighbors
fruit fly larval polytene chromosome
Drosophila
subobscura
cline
Populations of Drosophila subobscura are polymorphic for at least one inversion in
five of their six chromosomes and the frequency of the inversions in the
populations varies by altitude and latitude, forming clines
Drosophila subobscura Genetics
• Due to chance, a series of genes contributing to the
phenotype of body size became involved in a
heterozygotic inverted sequence
• One set of alleles, a multi-locus genotype, are
expressed to confer a consistent larger body size in
the flies
• Another set of alleles at the same inverted locus
contribute to small body size
Drosophila subobscura Genetics
• Natural selection
tends to eliminate
large flies in hot dry
climates and to
eliminate small flies
in cold wet climates
• Cold and wet climates are more common the
farther you move from the equator, whereas hot dry
climates are more common closer to the equator
• This becomes a stable microevolutionary
polymorphism
Inversion Frequencies Form Clines in
Drosophila subobscura
Est inversion favors
large body size
hot/dry
cold/wet
hot/dry
cold/wet
The two adapted genotypes are preserved in the two different climates because having
the genes tied up in a linkage group where cross-over is very unlikely means that the
population does not waste a lot of reproductive potential on offspring with a mixed
genotype and therefore a blended or intermediate phenotype
Instead, the populations show less variation in body size but the body size varies
appropriately with climate types
Condensation of Chromosomes in
Muntiacus sp.
Diploid chromosome sets of two species of muntjacs, small southeast Asian
relatives of deer (Moschidae: Artiodactyla: Mammalia): Muntiacus reevesi
(2n=46) (above) and Muntiacus muntiacus (2n=8) (below), both to the same
scale. Despite enormous differences in chromosome sizes and numbers, the
DNA content of cells in the two species and their morphological phenotypes
are very similar. Such changes in chromosome numbers can make speciation
and reproductive isolation easier.
Figure 05A: Chinese muntjac deer
Courtesy of Chuck Dresner/Saint Louis Zoo
(2n=46) (above) and (2n=8 )(below)
Figure 05B: Indian muntjac deer
Courtesy of the Saint Louis Zoo
Muntiacus muntjac (2n=6)
is mentioned in your text
Chromosomal Evolution in Primates
Figure 06: Banding arrangements of the chromosomes of
humans, chimpanzees, gorillas, and orangutans
• G-banding (Giemsa
stain) techniques
allow for a similar
reference set of
bands in other
normal chromosomes
• Common banding
patters imply close
evolutionary
relationships
Reproduced from Yunis, J. J., and Prakash, O. Science 215
(1982): 1525-1530. Reprinted with permission from AAAS.
Chromosomal Evolution in Primates
Figure 06: Banding arrangements of the chromosomes of
humans, chimpanzees, gorillas, and orangutans
• Notice that the
banding patterns are
very similar for all the
chromosomes of all
the apes
• Notice that humans
differ in having a
chromosome #2 that
appears to be fused
from two shorter ape
chromosomes
Reproduced from Yunis, J. J., and Prakash, O. Science 215
(1982): 1525-1530. Reprinted with permission from AAAS.
Mutations as a Source of
Genetic Variation
• Mutations are normally expressed at one of
two levels of gene activity
– Changes within a gene product, for example, in
the amino acid constitution of a particular protein
– Changes in the regulation of a gene or its product
• Mutations may affect the amount or rate at
which a gene product is produced, or whether
or not the protein is produced at all or at what
points in the life of the cell
Measuring Genetic Variation in Natural
Populations
• Phenotypic Variation
– anatomy
– biochemistry
– physiology
– development
– behavior
• Genotypic Variation
– alleles
– loci
– chromosomes
– genomes
In most cases, one cannot
infer a genotype just from
the inspection or identification
of a particular phenotype
Indirect evidence: proteins
Direct evidence: DNA
Evolutionary Impact of Mutations
• All mutation events increase
genetic variation in populations
and give natural selection the raw
material from which to generate
adaptive evolutionary changes
• Both the mutational processes
and their rates or frequencies are
diverse
• Evolution is driven by the
combination of both these
processes, mutation and
selection
variation in Acacia ligulata seeds
Evolutionary Impact of Mutations
• It is important to remember that most of mutational
processes lead to decreased adaptation most of the time
• Most mutations are harmful; most chromosome
rearrangements are harmful; most changes in ploidy are
harmful
• However, when you take the long view, when there are so
many species, so many individuals, and so much time (3.5
billion years), even low frequency events, such as beneficial
mutations, beneficial chromosomal rearrangements,
beneficial changes in genome ploidy can occur and when
they do, natural selection will be there as the mechanism
to see that they are preserved and spread
Gene Regulation
• Which genes are transcribed into messenger
RNA, which transcripts are translated into
proteins, and which proteins are activated, are
the result of interactions that often begin with
signals that initiate different genetic
regulatory pathways or networks
Table T02: Ways by Which Genetic
Variation is Maintained or Can Change at
the Level of Individual Genes
Gene Regulation as a Source of Variation
• Gene regulation in the bacterium Escherichia coli
• The Lac Operon (Jacob & Monod, 1961, earned
them the Nobel Prize in Physiology or Medicine in
1965)
Figure 08A: Scheme of lac enzyme synthesis in E. coli
Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985.
Gene Regulation as a Source of
Variation
lactose
Figure 08B: Scheme of lac enzyme synthesis in E. coli
Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985.
Figure 08C: Scheme of lac enzyme synthesis in E. coli
Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985.
Gene Regulation in Eukaryotic Cells
• Three major regulatory mechanisms control
transcription of DNA → mRNA:
– cis– trans– RNA interference (RNAi) - regulation
– Minor mechanisms
• Transposons
• Posttranscriptional modification
[ great animation
on RNAi action ]
Trans-Regulation
• The trans-regulatory elements are the DNA
sequences that encode Transcription Factors
(regulatory proteins)
• Trans-regulatory sequences reside on other
DNA molecules than the regulated gene
• These Transcription Factors (TF) can bind to
the cis-regulatory elements or the CAAT and
TATA boxes adjacent to a structural gene
Cis-Regulation
• Cis-regulatory elements reside upstream from a
promoter region for a structural gene on the same
DNA (chromosome)
• Transcription factors (promoters, enhancers,
silencers and repressors) bind to the cis-regulatory
elements to encourage or discourage transcription
of the structural gene
• Modification of cis- and trans- regulation are
important mechanisms leading to developmental
and morphological change in evolution
Cis- and Trans-Regulation
Figure B01A: cis-regulatory elements and gene transcription in animals
Figure B01B: cis-regulatory elements and gene transcription in animals
Adapted from Carroll et al. From DNA To Diversity, Second edition. Blackwell Publishing, 2005.
RNAi-Regulation
• Small interference RNA (siRNA) molecules and
microRNA (miRNA) molecules were discovered
relatively recently
• These short (~21 nucleotide molecules) have a
variety of roles in eukaryotes including
defense against viruses and transposable
elements, but also exert regulatory roles in
translation of proteins, cell division and cell
differentiation
RNAi-Regulation
RNAi silencing is initiated when double-stranded
RNA (dsRNA) is processed into small interfering
RNAs (siRNA) between 19-26 base pairs in length
by an RNaseIII enzyme called Dicer.
These siRNAs are subsequently incorporated into
RNA-induced silencing complexes (RISC) that
target complimentary messenger RNA (mRNA)
sequences for cleavage to mediate gene
suppression
Pre-mRNA: short stem-loop structures are formed when mRNAs are processed from
primary transcripts. The main function of siRNA is cleavage of miRNA. The main
function of miRNA is the inhibition of protein synthesis by blocking mRNA translation.
RNAi-Regulation
• Small interference RNA (siRNA) and microRNA
(miRNA) molecules can increase or decrease
the rate of translation
• They bind to messenger RNAs and cleave
them, halting transcription, when present
• They can act on multiple types of mRNA in a
cell so they can have wide-ranging effects
• Mutations in their loci can have profound
effects on phenotypes
RNAi-Regulation
• Because Small interference RNA (siRNA) and
microRNA (miRNA) molecules can be carried
by vectors (e.g., viruses) from one cell to
another, there has been recent speculation
that they could be agents for moving somatic
mutations to germ cells
• If so, this would be somewhat analogous to
Darwin’s idea of gemmules and pangenesis in
a modern form
• We’ll have to wait to see on that idea!
Posttranscriptional Modification
• Recall that in Eukaryotes, after a structural
gene is transcribed into pre-mRNA, it can be
modified in various ways
– Exons must be removed, and there can be options
as to which exons are removed (RNA editing)
– Addition of variable length poly-Adenine tails can
affect the lifespan of the mRNA in the cytoplasm
before it is degraded
– Modifiers can bind to the mRNA to delay or
prevent translation
Posttranscriptional Modification
• One of the best
studied examples is
in the gene libraries
vertebrates carry to
direct the synthesis
of millions of
different antibody
molecules
Light and Heavy Ab Chain
Recombination
Ig class switching
Estimates of Mutation Per Genome
Per Generation [Individual]
Short generation times
Only one cell division/generation
Long generation times
many cell division to produce gametes/generation
Estimations are based
on Nonsense
Mutations.
How Can Mutations Affect Fitness?
• While mutation rate at any given locus is
usually fairly low, since there are many
hundreds of genes in most organisms,
then a given individual organism is
actually fairly likely to acquire one or
mutations somewhere in its genome
• However, a mutation will only be passed
to offspring if the mutation occurs in the
germ cells leading to gamete production
How Can Mutations Affect Fitness?
• Each human being receives approximately 60 new
mutations in his/her genome from his/her parents (2011)
How Can Mutations Affect Fitness?
• A mutation acquired in any other cell is termed a
somatic mutation, and will not be a heritable
mutation, though it may have an impact on the
fitness of this individual, especially if it occurred
early in development, and therefore becomes
widespread in tissues or organs.
• That impact could be positive or, more likely,
negative. Why more likely negative?
• Because the normal allele or genotype has already
been refined and preserved by natural selection for
millions, perhaps billions of years, and most chance
mutations are likely to disrupt rather than improve
protein function if they have any effect at all.
How Do Most Mutations Affect Fitness?
• Photocopy Error: like the C. elegans
study, the accumulation of many small
errors leads to loss of function over
generations
10
20
50
75
100
How Do Most Mutations Affect Fitness?
Controls were normal worms experiencing
natural selection in a competitive lab environment.
Mutation Accumulation
lineages were reared in a
protected lab environment
where all survival needs
were provided
Caenorhabditis elegans is a small
(about 1 mm long) soil nematode found
in temperate regions
How Do Most Mutations Affect Fitness?
• There is a complex
interplay between
genotype, phenotype,
competition/survival
and reproduction
• A mutation may act at
one or more than one
level in the process
Evolutionary Developmental Biology
Hox
genes
• Edward B. Lewis discovered
homeotic genes in DNA in the 1990s
• Nobel Prize in Medicine (1995)
• This work led to the new
subdiscipline “Evo-Devo”
• Lewis laid the groundwork for our
current understanding of the
universal evolutionarily conserved
strategies controlling animal
development
Gene Regulation and Evolution
• A single change in a regulatory gene that controls
other genes can change how a gene network works,
with dramatic consequences for the phenotype
• Homeobox gene, Ultrabithorax
Figure
09B: Fly
with two
sets of
wings
Figure 09A: Normal fly with halteres
© Eye of Science/Photo Researchers, Inc.
Gene Regulation and Evolution
• Sonic hedgehog (Shh), Pax-6, and the
homeobox gene Prox1 interact in the
development of the Mexican tetra
• Increased Shh expression reduces eye
development but increases the number
of taste buds, compensating for
reduced vision with increased
chemoreception in the blind form
• Lateral line function is also expanded in
the blind form, but the gene locus is
unknown
Figure 11: Mexican tetra
Courtesy of Dr. Simon Walker, Department of
Zoology, University of Oxford
Figure 10B: Mexican cave fish
Adapted from Franz-Odendaal, T. A., and
B. K. Hall, Evol. & Devel 8 (2006): 94-100.
What Can a Mutation Do?
Poisonous plants can be
teratogens. For instance, the
skunk cabbage Veratrum
californicum, naturally found
Synpolydactyly (SPD) is a genetic disorder that results from growing in meadows of the Rocky
mutations in one of the HOX genes. The phenotypes are
mountains, can cause severe birth
shown in the pictures above, which usually involves
defects in the offspring of sheep
developmental disorders in the fingers and toes resulting
or cattle that have grazed on this
in fusion and malformation.
plant. These birth defects include
neurological damage and
cyclopia, the fusion of two eyes
into one. Humans and other
mammals are also susceptible to
this teratogen.
Transposable Elements
• Barbara McClintock (19021992)
• Discovered transposons and
gene regulation in maize
between 1944 and 1953
• Her work was ignored and
misunderstood for decades,
but . . .
• Nobel Prize for Physiology
or Medicine (1983)
Figure B02A: Mosaic color patterns Figure B02B: Mosaic color patterns of
of seeds in cobs of maize
seeds in cobs of maize
© Mike Flippo/ShutterStock, Inc.
© Greg30127/Dreamstime.com
Transposable Elements
• Transposons produce special transposase enzymes that
allow it to insert copies of itself into various target sites in
an organism’s nuclear genome
Transposable Elements
Figure 12: E. Coli-derived IS1 transposon into the maize genome
Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985.
It is probably best to think of Transposable Elements as molecular
parasites which may accidentally create adaptive (or harmful)
mutations and phenotypic variations, and act as agents of
Horizontal Gene Transfer in Eukaryotes. There is still much to be
learned about them.
Transposable Elements
• In primates, an Alu sequence is present in perhaps more
than thousands of copies in each diploid human cell, a
genetic synapomorphy for primates
Summary: Types of Mutation with
Significant Evolutionary Impact
In the cases of gene duplication and polyploidy, “extra” genes become
available to mutate, possibly providing new preadaptations/proteins, while
the original genes continue to code for the original functional proteins.
Mutations are Necessary for Evolution
Chapter 12
End
How Are Tetraploid Individuals
Produced in Plants?
• When a tetraploid individual
matures and produces
gametes by meiosis, haploid
gametes with the 2N
chromosome number form
easily and unite to produce
more tetraploid individuals.
hosta
Chromosomal Rearrangements
reciprocal crossover
•
Translocation chromosomes produce visible evidence of
the process of recombination during meiosis